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Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

2016년 4월 13일 업데이트: Mayo Clinic

Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis.

PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

OBJECTIVES:

Primary

  • Compare hematologic response rate in patients with primary systemic amyloidosis treated with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs high-dose melphalan followed by autologous stem cell transplantation.
  • Compare the toxicity of these regimens in these patients.

Secondary

  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the regression of organ involvement in patients treated with these regimens.
  • Compare the duration of response in patients treated with these regimens.
  • Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes in patients treated with these regimens.
  • Compare quality of life of patients treated with these regimens.
  • Compare the information-seeking behavior in patients treated with these regimens.

OUTLINE: This is a comprehensive cohort study comprising a randomized option and a nonrandomized option. Patients consenting to randomization are stratified by risk group (high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2 treatment arms. Patients not consenting to randomization choose their treatment arm.

  • Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA, and nucleotide sequence analysis to determine VH and VL gene families and carrier status. Urine is collected at baseline and analyzed for light-chain protein levels by exclusion chromatography.

Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study treatment, and then every 6 months for up to 5 years.

After completion of study treatment, patients are followed every 6 months for up to 10 years.

연구 유형

중재적

등록 (실제)

89

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Minnesota
      • Rochester, Minnesota, 미국, 55905
        • Mayo Clinic

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary systemic amyloidosis

    • Amyloid light-chain (AL) disease
  • Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio

  • The following amyloid syndromes* are allowed:

    • Amyloid hepatomegaly
    • Cardiomyopathy
    • Proteinuria
    • Peripheral or autonomic neuropathy
    • Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication
    • Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome
  • No secondary or familial amyloidosis
  • No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy
  • No multiple myeloma with > 30% plasma cells in the bone marrow
  • No amyloidosis manifested only by carpal tunnel syndrome or purpura

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 6 times ULN
  • Creatinine ≤ 3.0 mg/dL
  • No NYHA class IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for < 1 month

    • Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician
  • No concurrent participation in another clinical trial involving a pharmacologic agent

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
활성 비교기: Arm A

Patients receive low-dose melphalan IV over 15-30 minutes on day

1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses.

Study treatment beyond one year is not allowed.
의약품: 덱사메타손
구두로 주어진
의약품: melphalan
Given IV or orally
실험적: Arm B
Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
의약품: melphalan
Given IV or orally
생물학적: filgrastim
No administration information given
절차: 자가조혈모세포이식
0일에 제공

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Hematologic Response Rate
기간: 10 years

Response that was confirmed on 2 consecutive evaluations during treatment. A hematologic response consisted of a Complete response, Very Good Partial Response or Partial Response.

  • Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
  • Very Good Partial Response (VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.
  • Partial Response (PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
10 years

2차 결과 측정

결과 측정
측정값 설명
기간
3 Year Overall Survival
기간: 3 years
Percentage of patients who were alive at 3 years. The 3-year survival rate was estimated using the Kaplan Meier method.
3 years
Organ Response to Treatment
기간: 10 years

Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.

Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%.
10 years

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Mayo Clinic

협력자

National Cancer Institute (NCI)

수사관

  • 연구 의자: Morie A. Gertz, MD, Mayo Clinic

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2005년 10월 1일

기본 완료 (실제)

2012년 7월 1일

연구 완료 (실제)

2014년 12월 1일

연구 등록 날짜

최초 제출

2007년 5월 23일

QC 기준을 충족하는 최초 제출

2007년 5월 23일

처음 게시됨 (추정)

2007년 5월 24일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2016년 5월 17일

QC 기준을 충족하는 마지막 업데이트 제출

2016년 4월 13일

마지막으로 확인됨

2015년 6월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • CDR0000546745
  • P30CA015083 (미국 NIH 보조금/계약)
  • MC0482 (기타 식별자: Mayo Clinic Cancer Center)
  • 1691-05 (기타 식별자: Mayo Clinic IRB)
  • NCI-2009-01329 (레지스트리 식별자: NCI-CTRP)

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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스폰서 및 공동 작업자

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약물 개입

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정황

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약물 개입

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스폰서 / 협력자

위치

3
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